PROJECT SUMMARY Image-guidance has not been widely adopted in open lumbar fusion procedures because of cumbersome patient registration techniques. Accumulated mobility between vertebrae prohibits use of skin-affixed fiducials (requiring the surgeon to identify, expose, and localize anatomical landmarks within the surgical field), and registration at the start of surgery does not compensate for intervertebral motion between preoperative supine CT scans and intraoperative prone patient position. An automated registration procedure could accelerate adoption and improve outcomes, in addition to reducing costs, complexity, and x-ray dose associated with spine surgical guidance methods in current clinical use. Our target population is patients with symptomatic lumbar degenerative spondylolisthesis, where open decompression and fusion surgery, performed more than 300,000 times annually, improves patient-reported outcomes compared to non-surgical treatment. Image- guidance allows more accurate placement of pedicle screws, which could reduce revision rates and minimize patient harm, thereby allowing hospitals and surgeons to avoid reimbursement penalties from Medicare and other payers. We have developed an automated image-based intraoperative stereovision (iSV) to preoperative CT (pCT) registration that compensates for intervertebral motion, and have successfully applied the technique in two live animals, achieving excellent target registration errors (TREs less than 2.1 mm). We now propose to improve technical aspects of the approach in experimental studies and assess feasibility of this novel registration technology for clinical implementation. Specifically, we will (i) develop a portable iSV scanner as a radiation-free alternative to intraoperative CT (iCT) or O-arm, (ii) validate, evaluate and optimize the tehcnique in a systematic series of live animal surgeries, and (iii) translate the technology into a series of human cases of open lumbar fusion for degenerative spondylolisthesis. Comparisons of the new iSV approach to standard-of- care image-guidance with a commercial system (e.g., Medtronic StealthStation) and to high-fidelity navigation achieved with iCT will be performed to establish the relative performance improvements that can be obtained.